Myocardial Injury and Altered Gene Expression Associated With SARS-CoV-2 Infection or mRNA Vaccination

[Display omitted] •Patients with biomarker, imaging, or electrocardiographic evidence of myocardial injury associated with recent COVID-19 infection exhibited myocardial histopathologic findings ranging from myocarditis (n = 1) and nonspecific abnormalities (n = 4) to no abnormalities (n = 2).•Patients with myocardial injury associated with recent mRNA vaccination exhibited histopathologic findings of microvascular thrombosis (n = 1) and nonspecific abnormalities (n = 3).•Despite the variability in histopathologic findings, mRNA expression of candidate genes, selected for protein gene product likelihood of producing myocardial dysfunction, inflammation, or a prothrombotic state in response to Spike protein, exhibited similar changes, consisting of down-regulation in ACE2, ACE2/ACE ratio, AGTR1, and ITGA5 and up-regulation in ACE and F3 (tissue factor).•COVID-19 and post–mRNA vaccine myocardial injury may have a common molecular pathology. SARS CoV-2 enters host cells via its Spike protein moiety binding to the essential cardiac enzyme angiotensin-converting enzyme (ACE) 2, followed by internalization. COVID-19 mRNA vaccines are RNA sequences that are translated into Spike protein, which follows the same ACE2-binding route as the intact virion. In model systems, isolated Spike protein can produce cell damage and altered gene expression, and myocardial injury or myocarditis can occur during COVID-19 or after mRNA vaccination. We investigated 7 COVID-19 and 6 post–mRNA vaccination patients with myocardial injury and found nearly identical alterations in gene expression that would predispose to inflammation, coagulopathy, and myocardial dysfunction.